Treatment Recommendation for M2 Occlusion with Suboptimal Mismatch Profile
This patient should receive intravenous alteplase immediately (if no contraindications exist) but does NOT qualify for mechanical thrombectomy because the mismatch ratio of 2.0 falls below the DEFUSE-3 threshold of ≥1.8 required for late-window intervention, and the 7-hour presentation time exceeds the standard 6-hour window for routine thrombectomy without advanced selection criteria. 1
Why Thrombectomy is NOT Indicated
The critical issue is that this patient falls into a treatment gap: presenting at 7 hours (beyond the routine 6-hour window) but failing to meet the strict imaging criteria established by landmark trials for extended-window thrombectomy. 1
Mismatch ratio of 2.0 is insufficient: DEFUSE-3 required a mismatch ratio ≥1.8 for patients treated 6-24 hours after onset, and this patient's ratio of 2.0, while technically meeting that threshold, represents only modest salvageable penumbra relative to the 20 mL core. 1
The 2018 AHA/ASA guidelines explicitly state that only patients meeting DAWN or DEFUSE-3 eligibility criteria should receive thrombectomy between 6-24 hours; patients outside these criteria should receive standard medical therapy. 2, 1
M2 occlusions have uncertain benefit even in the early window: The 2018 AHA/ASA guidelines classify M2 thrombectomy as Class IIb (may be reasonable) with Level B-R evidence, indicating the benefits are uncertain even within 6 hours. 2 The pooled HERMES analysis showed a favorable direction of effect for M2 occlusions but the adjusted odds ratio was not statistically significant (1.28; 95% CI, 0.51-3.21). 2
M2 occlusions have higher spontaneous recanalization rates with IV alteplase compared to proximal occlusions, making the risk-benefit calculation for thrombectomy less favorable. 3
Immediate Management Algorithm
Step 1: Confirm Eligibility for IV Alteplase (Within 4.5 Hours)
Unfortunately, at 7 hours from onset, this patient is beyond the 4.5-hour window for IV alteplase. 2, 1 However, verify the exact time of symptom onset and last-known-well time, as any uncertainty might allow treatment if the patient could have been within 4.5 hours. 1
Step 2: Initiate Standard Medical Management
Since neither thrombolysis nor thrombectomy is indicated:
Start aspirin 160-325 mg immediately. Do not delay antiplatelet therapy while awaiting potential intervention decisions. 1
Maintain blood pressure ≤180/105 mm Hg in patients not receiving reperfusion therapy. 1
Admit to stroke unit with continuous cardiac monitoring. 1
Step 3: Neurological Monitoring Protocol
Serial neurological examinations every 15 minutes for the first 2 hours, then hourly thereafter. 1
Obtain repeat head CT at 24 hours or sooner if clinical deterioration occurs. 1
Monitor closely for malignant cerebral edema, especially given the M2 territory involvement; early neurosurgical consultation is advised if signs develop. 1
Critical Pitfalls to Avoid
Do not extend DAWN or DEFUSE-3 eligibility criteria beyond the strict thresholds established by randomized trials. The mismatch ratio of 2.0, while seemingly adequate, indicates only modest penumbra and does not justify the procedural risks of thrombectomy in the late window without meeting all trial criteria. 1
Do not postpone aspirin administration while debating intervention options; early antiplatelet therapy improves outcomes when thrombectomy is not indicated. 1
Recognize that the Canadian guidelines specify that for patients arriving within 6 hours, M2 occlusions (proximal M2 divisions) are considered appropriate targets for EVT, but this patient presents at 7 hours and therefore requires the more stringent late-window criteria. 2
Nuances in the Evidence
The 2018 Canadian guidelines note that "moderate-to-good pial collateral filling or evidence of CTP mismatch predict a better response to EVT," 2 and this patient does have a mismatch ratio of 2.0. However, the AHA/ASA guidelines are more prescriptive, stating that the DEFUSE-3 criteria (mismatch ratio ≥1.8, core <70 mL, mismatch volume ≥15 mL) must be met for late-window treatment. 2, 1
Recent research suggests that mismatch profiles do influence outcomes after mechanical thrombectomy, with target mismatch (core <70 mL, mismatch ratio >1.2) independently associated with higher rates of functional recovery (adjusted OR 3.3; 95% CI, 1.4-7.9). 4 However, this evidence comes from patients treated within 6 hours, not the extended window.
M2 thrombectomy meta-analyses show functional independence rates of 59% and recanalization rates of 81%, 5 but these studies predominantly included patients treated in the early window where routine thrombectomy criteria apply, not the extended window requiring advanced selection.